Abstract
Although the contribution of carbohydrate catabolism to bacterial colonization and infection is well recognized, the transcriptional changes during these processes are still unknown. In this study, we have performed comparative global gene expression analysis of GBS in sugar-free versus high glucose milieu. The analysis revealed a differential expression of genes involved in metabolism, transport and host-pathogen interaction. Many of them appeared to be among the genes previously reported to be controlled by the CovRS two-component system. Indeed, the transcription profile of a ΔcovRS strain grown in high-glucose conditions was profoundly affected. In particular, of the total genes described to be regulated by glucose, ∼27% were under CovRS control with a functional role in protein synthesis, transport, energy metabolism and regulation. Among the CovRS dependent genes, we found bibA, a recently characterized adhesin involved in bacterial serum resistance and here reported to be down-regulated by glucose. ChIP analysis revealed that in the presence of glucose, CovR binds bibA promoter in vivo, suggesting that CovR may act as a negative regulator or a repressor. We also demonstrated that, as for other target promoters, chemical phosphorylation of CovR in aspartic acid increases its affinity for the bibA promoter region. The data reported in this study contribute to the understanding of the molecular mechanisms modulating the adaptation of GBS to glucose.
Highlights
Streptococcus agalactiae (GBS) is a Gram-positive b-haemolytic human pathogen commonly residing in the gastrointestinal tract of up to 50% of the healthy population
Regulation of GBS gene expression by glucose To elucidate the response of GBS to glucose, we performed a comparative global gene expression analysis of the 2603 V/R GBS grown in THB until late exponential phase, centrifuged and grown up to mid exponential phase in a peptone-based complex medium (CM) before been transferred for 30 minutes in a CM devoid of sugars or containing 55 mM glucose
Glucose and other carbon sources are known to influence the lifestyle of many pathogens that adapt their metabolism to the nutritional composition of their host niches
Summary
Streptococcus agalactiae (GBS) is a Gram-positive b-haemolytic human pathogen commonly residing in the gastrointestinal tract of up to 50% of the healthy population. GBS is commonly associated with neonatal diseases [1] and postpartum infections, it is an important cause of morbidity and mortality among adults [2]. The impact of hyperglycemia upon susceptibility to GBS infection has not been fully elucidated, at least in part, this effect seems to be due to impairment of neutrophil effector functions [9]. This is supported by clinical evidence indicating a strong correlation between individuals with high blood glucose levels and the propensity to acquire GBS systemic infections [6,7]. A clear link between virulence factor production and complex carbohydrate catabolism in Streptococcus pneumoniae, Streptococcus pyogenes and GBS has been recently proposed by Shelburne and colleagues [11]
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